It is generally agreed that DNA damage and repair play a major role in the fate of living cells in terms of viability, mutagenesis and carcinogenesis, and aging. Skin cells are subject to continuous assaults by solar radiation, of which UVB is responsible for sunburns and skin cancer, while UVA is tanning. Both ranges of UV light are known to produce specific photoproducts, such as thymine dimers and the 6-4 photoproduct, and UVA has been shown to affect DNA strand breaks, in addition to formation of photoproducts, particularly as a result of attacks by reactive oxygen species.
The mechanism of excision repair, the major repair mechanism of damaged DNA, has been discovered in 1963 by Riklis (1964, 1965),(1),(2), Setlow and Carrier(3), (1964), and Boyce and Howard-Flanders (1964)(4). Since then, the generality of this repair pathway, as predicted by Riklis, was confirmed for many types of healthy cells and for different types of radiations, such as ultraviolet and ionizing radiations. Other modes of repair have been identified, including postreplication repair and strand break repair by ligation, and thus DNA damage and repair have become a most important event in cellular biology.
In 1981, Riklis(1)(2) had shown the possibility of enhancing DNA repair by the radioprotective compound WR-2721. He later showed the possibility of enhancing DNA repair by other chemical compounds, such as the vitamin nicotinamide.
The fact that ultraviolet assault on cells results in the formation of photoproducts is long known. In 1960 Beukers and Berends(5) identified thymine dimers (T&lt;&gt;T) as the product of irradiation of frozen thymine solutions with short UV radiation. In 1961 Wacker(6) identified T=T as the major photoproduct of UVC radiation which is responsible for cell death. It being the substrate of repair by photoreactivation was shown in 1962 by Rupert.
In 1963, as mentioned, thymine dimer was shown to be excised from DNA during the process of excision repair (Riklis(1)(2) Setlow & Carrier(3) Boyce & Howard-Flanders(4)). Other photoproducts have also been identified by various authors (Wang(7), Riklis(8) et al). A unique photoproduct was discovered by Riklis in DNA irradiated in a dry state, and a year later this product was found in spores and named the "spore product" (Setlow & Carrier(3)).
The excision repair pathways exist in normal healthy cells of mammals, plants and bacteria. Mutant bacteria exist which are deficient in repair, and in parallel there are human diseases which are manifested in extreme sensitivity to sun light (xeroderma pigmentosum) or to ionizing radiation (ataxia telangiectasia) and are deficient in cell ability to repair DNA.